Nude mice, which are congentially athymic, will not reject xenografts of human normal or neoplastic tissues including normal lymphoid tissues. It should thus be possible to create chimeric nude mice whose lymphoid system has been replaced by human cells. This will be accomplished by total body irradiation of nude mice (400-800 R) followed by reconstitution with adult human bone previously depleted of T-cells. T-cell depletion will be done by incubation of bone marrow cells with guinea pig or rabbit complement and monoclonal antibody to pan-T-cell determinants (anti-Leu-1 or OKT3). These antibodies have been shown to inhibit MLC, an in vitro corollary of graft versus host disease, and thus T-cell depletion should lead to the establishment of stable chimeras. Reconstitution with grafted cells will be monitored by histology of lymph nodes and spleens and by the number of cells reactive with monoclonal antibody to HLA-A,B,C (W6/32). Establishment of stable chimeras will then allow lateral grafting of chimeric spleen cells to other nude mice. These animals can then be utilized in a variety of studies to: 1) determine the effect of thymic reconstitution on the chimeric state, (a) induction of tolerance to preexisting xenografts and (b) reconstitution of T-dependent responses; 2) determine whether tumor antigens defined by monoclonal antibodies can function as transplantation rejection antigens; and 3) develop human-human monoclonal antibodies to tumor associated antigens.